Aurora-A kinase nuclear expression in chronic lymphocytic leukemia.
Aurora-A kinase is a cell-cycle-regulating kinase required for chromosomal segregation. Overexpression of Aurora-A kinase has been shown to correlate with tumor proliferation and chromosomal instability. We investigated Aurora-A kinase expression in peripheral blood and bone marrow of 47 chronic lymphocytic leukemia patients and 20 age-matched hematologically healthy subjects. Western blot analysis showed significantly higher Aurora-A levels in chronic lymphocytic leukemia (42 of 47) compared with lymphocytes of healthy subjects. However, Aurora-A mRNA expression in three chronic lymphocytic leukemia patients was similar to or lower than that of healthy control subjects. In 28 of 42 chronic lymphocytic leukemia patients with elevated Aurora-A kinase expression, one or more chromosomal abnormalities were detected, including trisomy 12 in 9 patients and deletion of the ataxia telangiectasia-mutated gene in 9 patients. Aurora-A was also detected in all (100%) chronic lymphocytic leukemia cases by immunohistochemistry, with a nuclear staining pattern. The larger prolymphocytes and paraimmunoblasts showed stronger Aurora-A kinase expression than did small lymphocytes. In contrast, normal bone marrow reactive lymphocytes were negative for Aurora-A with positive histiocytes and immature myeloid cells. Immunostaining for acetylated histone H3 showed a nuclear pattern in all 38 chronic lymphocytic leukemia cases and double labeling showed coexpression of acetylated histone H3 and Aurora-A. In summary, Aurora-A kinase is overexpressed in chronic lymphocytic leukemia cells. The expression of acetylated histone H3 suggests that Aurora-A kinase may be active (functional). Thus, Aurora-A kinase overexpression in chronic lymphocytic leukemia may be involved in the genesis of chromosomal abnormalities and is a potential target for therapeutic intervention.
Inamdar
Kedar V
KV
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
O'Brien
Susan
S
Sen
Subrata
S
Keating
Michael
M
Nguyen
Martin H
MH
Wang
Xuemei
X
Fernandez
Michael
M
Thomazy
Vilmos
V
Medeiros
L Jeffrey
LJ
Bueso-Ramos
Carlos E
CE
D000107:Acetylation; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064127:Aurora Kinases; D015153:Blotting, Western; D002467:Cell Nucleus / Q000201:enzymology; D002869:Chromosome Aberrations; D005260:Female; D005434:Flow Cytometry; D006657:Histones / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D006657:Histones; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases